pk sub-study of quilt-3.032 (ca alt-803-01-16) and of quilt-2.005 (ca alt-803-01-14)

Conditions: Pharmacokinetics

Summary: non-interventional pk sub-study of quilt-3.032 (ca-alt-803-01-16) and quilt-2.005 (ca-alt-803-01-14)

quilt-3.032 is a phase 2, open-label, single-arm, three-cohort, multicenter study of intravesical bcg plus alt-803 in patients with bcg unresponsive high grade nmibc. patients will be enrolled into one of three study cohorts. cohort a will enroll 80 patients who have histologically confirmed presence of bcg-unresponsive carcinoma in situ (cis) \[with or without ta or t1 disease\]. cohort b will enroll 80 patients who have histologically confirmed bcg-unresponsive high-grade ta or t1 disease. cohort c will enroll up to 23 patients who also have histologically confirmed presence of bcg-unresponsive cis \[with or without ta/t1 papillary disease\]. patients in cohorts a and b will receive alt-803 plus bcg combination treatment. patients in cohort c will receive alt-803 alone. enrollment of cohort c will start once the enrollment of cohort a is complete. cohorts a, b, and c are independent study cohorts and will be separately evaluated for efficacy. all patients treated in the study will receive via a urinary catheter in the bladder, bcg plus alt-803 or alt-803 alone weekly for 6 consecutive weeks during the induction treatment period. quilt-2.005 is a phase 2b, randomized, two-cohort, open-label, multicenter study of intravesical alt-803 plus bcg versus bcg alone, in bcg naïve patients with high-grade nmibc. patients will be enrolled into one of two study cohorts and randomized into two arms to be treated with either alt-803 plus bcg or bcg alone. cohort a will initially enroll 366 patients who have histologically confirmed cis (with or without ta/t1 papillary disease). cohort b will initially enroll 230 patients who have histologically confirmed high-grade papillary ta/t1 disease only. cohorts a and b are two independent study cohorts and will be evaluated separately for efficacy. pk sub-study: blood samples to determine serum levels of alt-803 will be collected on study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study week 1 and again at the same time points for study week 6. six subjects from either cohort a (either study) or cohort c (quilt 3.032) and six subjects from cohort b (either study) will be sampled initially. up to an additional 4 subjects for each cohort may also be sampled. patients enrolled in quilt 2.005 must have been randomized to receive alt-803 plus bcg to be eligible for the pk sub-study.

Eligibility criteria:
inclusion criteria: * only subjects who are eligible for and have entered into protocol quilt-3.032 or quilt-2.005 may participate in this sub-study. * patients enrolled in quilt-2.005 must have been randomized to receive alt-803 plus bcg to participate in this sub-study. exclusion criteria: * refusal to provide voluntary written informed consent and hipaa authorization and agree to comply with all protocol-specified procedures and follow-up evaluations. * loss of ≥ 475 ml blood volume or blood transfusion of any blood product within 3 months prior to screening.